Eccrine Carcinoma

Idrissi Serhrouchni et al. Diagnostic Pathology 2013, 8:15 http://www.diagnosticpathology.org/content/8/1/15

CASE REPORT Open Access Eccrine carcinoma : a rare cutaneous neoplasm Karima Idrissi Serhrouchni1*, Taoufiq Harmouch1, Laila Chbani1, Hind El Fatemi1, Mohammed Sekal1, Nawal Hammas1, Meriem Soughi2, Loubna Benchat2 and Afaf Amarti1

Abstract Eccrine carcinoma is an extremely rare malignancy of the skin with few well documented cases reported in the literature. It is frequently found on the lower extremities, and it equally affects both sexes in the sixth and seventh decade. In our case, we present a 46- year-old female with a recurring exophytic tumor on the right lower extremity, without local extension. The initial tumor was biopsied, excised and diagnosed as an eccrine carcinoma. Virtual Slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/ vs/3568051328673318. Keywords: Eccrine carcinoma, Sweat gland tumor, Mammary gland

Background Tumor markers as like as CA 19–9, CA 125, CA 15–3 Malignant cutaneous adnexal neoplasms are a large and va- were normal. MRI of the leg showed a subcutaneous ried group, in particular eccrine carcinoma. They are one of infiltrative process coming into contact with the muscle the most challenging areas of Dermatopathology [1]. fascia. Eccrine and apocrine neoplasms present a bewildering The rest of the radiological examination, including radiog- array of morphologies which often defy precise classifi- raphy of the lung, abdominopelvic ultrasonography, com- cation [2]. puted tomographic thoraco-abdomino-pelvic scan, was The purpose of this case is to discuss the most common normal. problems concerning the classification of this rare neoplasm The mammography and ultrasound examination objecti- and report the aim of the immunohistochemical profiles in fied a 4 mm measuring benign cystic lesion of the left breast differential diagnosis between a primitive eccrine carcinoma classified ACR 3, requiring supervision during six months. of the skin and a secondary neoplasm. After biopsy of the lesion, a surgical excision with clear margins was performed. On gross examination, the tumor was 15 cm in size, Case report bourgeoning, erythematous and heterogeneous with In July 2012, a 45-year-old Moroccan woman presented areas of necrosis and haemorrhage. to the department of Dermatology of Hassan II Univer- Microscopic examination of the specimen revealed an sity Hospital of Fez with a 25-year-history of primary undifferentiated malignant proliferation with nodular infertility, and an 18-month-history of an exophytic mass architecture, located in the deep dermis (Figure 2). at the posterior right lower extremity, gradually increas- Tumor cells made clear cytoplasm with an hyperchro- ing in size. She was otherwise healthy and had no matic nucleus and a high mitotic activity (Figure 3). systemic symptoms. Physical examination showed an ul- Immunohistochemical analysis showed positive stain- cerative and bourgeoning mass of 15 cm with bleeding ing for cytokeratine and progesterone receptor. Cytoke- and purulent features (Figure 1). Biological tests ratine 7 was weakly positive and Ki67 was estimated at included a complete blood count, routine blood and 95% (Figure 4). urine chemistry were normal, except for elevated LDH. In contrast, the tumor cells were not reactive to cyto- * Correspondence: [email protected] keratine 20, estrogen receptor, LCA, CD10, S 100 1Department of Pathology, Hassan II University Hospital, Fez 30000, Morocco Full list of author information is available at the end of the article

© 2013 Idrissi Serhrouchni et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Idrissi Serhrouchni et al. Diagnostic Pathology 2013, 8:15 Page 2 of 4 http://www.diagnosticpathology.org/content/8/1/15

sweat gland adenoma [5]. Such an approach, however, poses several problems; for example, (1) some carcinomas have no benign counterpart and do not fit the scheme (ductal carcinoma, adenoid cystic carcinoma, and mucinous carcinoma); (2) poorly differentiated carcinomas can be diagnosed only when a contiguous adenoma is found histologically; (3) histologic classification can be very complicated because adenomas are nume- rous and their classification is complex; and (4) terminology includes unusual and difficult terms, deriving from the terminology used for adenomas (malignant acrospiroma, porocarcinoma, hidradenocarcinoma, malignant cylindroma, malignant spiradenoma, and syrin- gocystadenocarcinoma) [6-9]. Recently, a classification of sweat gland carcinomas Figure 1 Clinical picture showed an ulcerative and bourgeoning mass of 15 cm with bleeding and purulent designed based on the classification of breast carcinomas features on the posterior right lower extremity. has been tentatively proposed [9]. Finally, recent studies have classified sweat gland carcinomas into eccrine and apocrine tumors [8,9]. In protein, HMB45, desmin, H-caldesmon, CD 99, CD 117, addition, no established authentic criteria are available CD 31 and CD 34. for differentiation of an eccrine from an apocrine tumor Based on these data, the diagnosis of primary cutane- [10]. Moreover, both eccrine and apocrine forms seem ous eccrine carcinoma was retained. to exist in some categories [5,9,11,12]. The correct identification of the origin of tumor is of Discussion utmost importance for the determination of appropriate Eccrine glands are directly developed from the em- therapy and prognosis. Immunohistochemistry has bryonic epidermis in the early months of fetal develop- proved to be a useful adjunct for this purpose [13]. ment [1]. They are widely distributed almost everywhere The cells in the excretory coil of eccrine gland sweat on the skin [2]. The topographic distribution of adnexal express positivity for low molecular weight keratin, epi- structures also offers insight into the logical classifica- thelial membrane antigen (EMA) and carcinoembryonic tion of adnexal neoplasms [3,4]. antigen (CEA), as well as S100 protein in the basal layer Microscopy alone is insufficient to establish eccrine only. The myoepithelial cell layer may be highlighted by lineage neoplasm because there are none specific micro- smooth muscle actin (SMA), p63 and calponin. Acrosy- scopic features [3]. ringeal cells stain for high molecular weight keratin and Some problems are related to the classification of cytokeratin 14. A subpopulation of cells also expresses sweat gland carcinomas, which are currently classified positivity to bcl-2 [2]. Some eccrine carcinomas are posi- on the basis of the corresponding classification of benign tif to estrogen and progesterone receptors wich has an important clinical implications, as affected patients may be partially treated with hormonal therapy [14]. The Ki- 67 and p53 may be used to differentiate benign from malignant lesions [15]. Clinically, eccrine carcinoma must be considered in the differential diagnosis of patients older than fifty years with long standing tumors in the limbs, including basal cell carcinoma (BCC), Paget’s disease, melanoma, metastatic cancer [16], inflammatory, lymphocytic and vascu- lar lesions [17]. The histopathology of mucinous eccrine carcinoma of the skin is analogous to that of its counterpart in the breast. Consequently, it is sometimes difficult to exclude a metastatic disease [15,18]. In a comparison between Figure 2 An undifferentiated malignant proliferation with primary sweat gland tumors and metastatic breast car- nodular architecture, located in the deep dermis (hematoxylin- cinoma to skin, Busam et al. [13,19] found that the use eosin, original magnification: x 100). of antibodies against epidermal growth factor receptor Idrissi Serhrouchni et al. Diagnostic Pathology 2013, 8:15 Page 3 of 4 http://www.diagnosticpathology.org/content/8/1/15

Figure 3 Tumor cells made clear cytoplasm with an hyperchromatic nucleus and a high mitotic activity (hematoxylin-eosin, original magnification: A, × 200, B, x 400).

strongly decorated 81% of sweat gland tumors, but only diagnosis of adnexal cancer; in their study, none of the 17% of metastatic breast cancers (P=0.001). There was examples of metastatic adenocarcinoma to skin stained no significant difference between the skin tumors and for p63, whereas virtually all the adnexal carcinomas metastatic breast carcinoma when antibodies against es- were positive. trogen and progesterone receptors were used, but with These studies showed that immunohistochemistry progression of disease, androgen receptors (AR) are pre- does not distinguish cutaneous eccrine tumours from served with higher frequency than ER/PR in metastatic cutaneous metastases of breast carcinoma, in which case mammary carcinoma [13]. In another study comparing clinical and radiological correlation is critical [24]. benign, malignant primary eccrine and apocrine neo- Other differential diagnoses comprise neoplasms with plasms to metastatic breast carcinoma, only 3.5% of clear cell differentiation. These include trichilemmal car- these primary adnexal cancers demonstrated HER-2 cinoma, clear cell BCC and clear cell carcinomas meta- positivity, whereas 10–23% of the breast carcinomas static to the skin. With respect to the latter, the were positive [13,20]. The authors suggested that this dominant diagnostic considerations are metastatic clear test may be useful in distinguishing primary skin cancers cell carcinoma from thyroid gland and lung. The ex- from metastatic breast cancers [20]. Another study pression of TTF seen in the great majority of these cases showed that primary cutaneous neoplasms stained is helpful in resolving this dilemma. Some metastatic strongly for p63 and CK 5/6 with high specificity, while thyroid cancers also manifest expression of thyroglobu- CK 7 and 20 were not useful [15,21]. When CK 7 was lin. Metastatic clear cell carcinoma of renal primary ori- positive in the cutaneous lesions, it exhibited marked gin manifests a prominent stromal vascularity with focality and a specific pattern, while metastatic breast hemorrhage and areas of granular necrosis typically evi- carcinoma expressed CK 7 diffusely and did not express dent in biopsy material. Clear cell squamous cell carci- p63 or CK 5/6. The usefulness of CK 5/6 was again noma of the cervix is a glycogen-rich cancer with shown by Plumb et al. [15,22]. Ivan et al. [15,23] pre- intercellular bridge formation characteristic of squa- sented further evidence of the usefulness of p63 in the mous differentiation [15].

Figure 4 Immunohistochemical study showing reactivity for CK (A), CK7 (B) and progesterone receptors (C). Idrissi Serhrouchni et al. Diagnostic Pathology 2013, 8:15 Page 4 of 4 http://www.diagnosticpathology.org/content/8/1/15

Conclusion 18. Page DL, Anderson TJ, Sakamoto G: Infiltrating carcinoma: major Eccrine carcinoma should be considered in the diagnosis histological types.InDiagnostic Histopathology of the Breast. Edited by Page DL, Anderson TJ. Churchill-Livingstone: New York; 1987:193–295. of cutaneous malignant tumor with immunostaining for 19. Busam KJ, Tan LK, Granter SR: Epidermal growth factor, estrogen, and CK7, P63, CK5/6, estrogen and progesterone receptors. progesterone receptor expression in primary sweat gland carcinomas and primary and metastatic mammary carcinomas. Mod Pathol 1999, 12:786–793. Consent from the patient 20. Hiatt KM, Pilow JL, Smoller BR: Her-2 expression in cutaneous eccrine and Written informed consent was obtained from patient for apocrine neoplasms. Mod Pathol 2004, 17:28–32. publication of this case report. 21. Qureshi HS, Ormsby AH, Lee MW: The diagnostic utility of p63, CK5/6, CK 7, and Ck 20 in distinguishing primary cutaneous adnexal neoplasms from metastatic carcinomas. Cutan Pathol 2004, 31:145–152. Abbreviations 22. Plumb SJ, Argenyi ZB, Stone MS: Cytokeratin 5/6 immunostaining in LDH: Lactate Dehydrogenase; MRI: Magnetic Resonance Imaging; cutaneous adnexal neoplasms and metastatic adenocarcinoma. ACR: American College of Radiology; CK: Cytokeratin; LCA: Leukocyte Am J Dermatopathol 2004, 26:447–451. Common Antigen. 23. Ivan D, Hafeez Diwan A, Prieto VG: Expression of p63 in primary cutaneous adnexal neoplasms and adenocarcinoma metastatic to the Competing interests skin. Mod Pathol 2005, 18:137–142. The authors declare that they have no competing interests. 24. Wallace ML, Longacre TA, Smoller BR: Estrogen and progesterone receptors and anti-‐gross cystic disease fluid protein 15 (BRST-‐2) fail to ’ Authors contributions distinguish metastatic breast carcinoma from eccrine neoplasms. All authors read and approved the final manuscript. Mod Pathol 1995, 8:897–901. Author details doi:10.1186/1746-1596-8-15 1Department of Pathology, Hassan II University Hospital, Fez 30000, Morocco. Cite this article as: Idrissi Serhrouchni et al.: Eccrine carcinoma : a rare 2Department of Dermatology, Hassan II University Hospital, Fez 30000, cutaneous neoplasm. Diagnostic Pathology 2013 8:15. Morocco.

Received: 9 December 2012 Accepted: 27 January 2013 Published: 4 February 2013

References 1. Montagna W: Embryology and anatomy of the cutaneous adnexa. J Cutan Pathol 1984, 11:350–351. 2. Nidal A, Khaled O, Danny G: Skin adnexal neoplasms: an approach to tumours of cutaneous sweat glands. J Clin Pathol 2007, 60:145–159. 3. Timothy H, Calmont M: Batman and adnexal neoplasms. J Cutan Pathol 2010, 37:401–402. 4. Brownstein MH, Shapiro L: The sweat gland adenomas. Int J Dermatol 1975, 14:397–411. 5. Carmelo U, Roberto B, Milena P, Adriana S, Chiara A, Augusto G: Carcinomas of Sweat Glands. Arch Pathol Lab Med 2001, 125:498–505. 6. Cooper PH: Carcinomas of sweat glands. Pathol Annu 1987, 22:83–110. 7. Santa C: Sweat glands carcinomas: a comprehensive review. Semin Diagn Pathol 1987, 4:38–74. 8. Murphy GF, Elder DE: Non-melanocytic Tumors of the Skin. Washington, DC: Armed Forces Institute of Pathology; 1991:61–153. Atlas of Tumor Pathology; 3rd series, fascicle 1. 9. Requena L, Kiryu H, Ackerman AB: Neoplasms With Apocrine Differentiation. Philadelphia, Pa: Lippincott-Raven; 1998:589–855. 10. Abenoza P, Ackerman AB: Neoplasms With Eccrine Differentiation. Philadelphia, Pa: Lea and Febiger; 1990:371–412. 11. Swanson PE, Mazoujian G, Mills SE, Campbell RJ, Wick MR: Immunoreactivity for estrogen receptor protein in sweat gland tumors. Am J Surg Pathol 1991, 15:835–841. 12. Ansai S, Koseki S, Hozumi Y, Kondo S: An immunohistochemical study of lysozyme, CD-15 (Leu M1), and gross cystic disease fluid protein-15 in Submit your next manuscript to BioMed Central various skin tumors: assessment of the specificity and sensitivity of markers of apocrine differentiation. Am J Dermatopathol 1995, 17:249–255. and take full advantage of: 13. Vinod B, Richard A, Jinobya K: Androgen receptor expression in metastatic adenocarcinoma in females favors a breast primary. Diagn Pathol 2006, • Convenient online submission 1:34. • Thorough peer review 14. Mirza I, Kloss R, Sieber SC: Malignant eccrine spiradenoma. Arch Pathol Lab Med 2002, 126:591–594. • No space constraints or color ﬁgure charges 15. Crowson AN, Magro CM, Mihm MC: Malignant adnexal neoplasms. • Immediate publication on acceptance Mod Pathol 2006, 19:93–126. • Inclusion in PubMed, CAS, Scopus and Google Scholar 16. Oliver C, Ashraf E, Bernard R, Armand A, Nadeem C: Eccrine porocarcinoma of the lower extremity: a case report and review of literature. World J • Research which is freely available for redistribution Surg Oncol 2011, 9:94. 17. Helena PS, Ventura MP, Orellana ME, Novais GA, Cheema DP, Burnier MN: Submit your manuscript at Histopathological study of lesions of the caruncle: a 15-year single www.biomedcentral.com/submit center review. Diagn Pathol 2009, 4:29.